Format

Send to

Choose Destination
Diabetes. 2016 Nov;65(11):3440-3452. Epub 2016 Aug 25.

Adipose Recruitment and Activation of Plasmacytoid Dendritic Cells Fuel Metaflammation.

Author information

1
Division of Cancer Biology and Inflammatory Disorders, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
2
Division of Cell Biology and Physiology, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
3
Department of Rheumatology, Institute of Postgraduate Medical Education and Research, Kolkata, India.
4
ILS Hospitals, Kolkata, India.
5
Zentrum Allergie und Umwelt, Technical University of Munich and Helmholtz Centre Munich, Munich, Germany.
6
Department of Endocrinology, Institute of Postgraduate Medical Education and Research, Kolkata, India.
7
Division of Cancer Biology and Inflammatory Disorders, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India dipyaman@iicb.res.in.

Abstract

In obese individuals, visceral adipose tissue (VAT) is the seat of chronic low-grade inflammation (metaflammation), but the mechanistic link between increased adiposity and metaflammation largely remains unclear. In obese individuals, deregulation of a specific adipokine, chemerin, contributes to innate initiation of metaflammation by recruiting circulating plasmacytoid dendritic cells (pDCs) into VAT through chemokine-like receptor 1 (CMKLR1). Adipose tissue-derived high-mobility group B1 (HMGB1) protein activates Toll-like receptor 9 (TLR9) in the adipose-recruited pDCs by transporting extracellular DNA through receptor for advanced glycation end products (RAGE) and induces production of type I interferons (IFNs). Type I IFNs in turn help in proinflammatory polarization of adipose-resident macrophages. IFN signature gene expression in VAT correlates with both adipose tissue and systemic insulin resistance (IR) in obese individuals, which is represented by ADIPO-IR and HOMA2-IR, respectively, and defines two subgroups with different susceptibility to IR. Thus, this study reveals a pathway that drives adipose tissue inflammation and consequent IR in obesity.

PMID:
27561727
DOI:
10.2337/db16-0331
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center